• Title/Summary/Keyword: pathway analysis

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Prediction of functional molecular machanism of Astragalus membranaceus on obesity via network pharmacology analysis (네트워크 약리학을 통한 황기의 항비만 효능 및 작용기전 예측 연구)

  • Mi Hye, Kim
    • The Korea Journal of Herbology
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    • v.38 no.1
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    • pp.45-53
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    • 2023
  • Objectives : Network pharmacology-based research is one of useful tool to predict the possible efficacy and molecular mechanisms of natural materials with multi compounds-multi targeting effects. In this study, we investigated the functional underlying mechanisms of Astragalus membranaceus Bunge (AM) on its anti-obesity effects using a network pharmacology analysis. Methods : The constituents of AM were collected from public databases and its target genes were gathered from PubChem database. The target genes of AM were compared with the gene set of obesity to find the correlation. Then, the network was constructed by Cytoscape 3.9.1. and functional enrichment analysis was conducted to predict the most relevant pathway of AM. Results : The result showed that AM network contained the 707 nodes and 6867 edges, and 525 intersecting genes were exhibited between AM and obesity gene set, indicating that high correlation with the effects of AM on obesity. Based on GO biological process and KEGG Pathway, 'Response to lipid', 'Cellular response to lipid', 'Lipid metabolic process', 'Regulation of chemokine production', 'Regulation of lipase activity', 'Chemokine signaling pathway', 'Regulation of lipolysis in adipocytes' and 'PPAR signaling pathway' were predicted as functional pathways of AM on obesity. Conclusions : AM showed high relevance with the lipid metabolism related with the chemokine production and lipolysis pathways. This study could be a basis that AM has promising effects on obesity via network pharmacology analysis.

Development of a Critical Pathway for Patients with Lumbar Laminectomy (요추척추궁 절제술 환자의 표준관리지침서 개발)

  • Park, Jae Jung;Park, Hyoung Sook
    • Korean Journal of Adult Nursing
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    • v.12 no.4
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    • pp.517-532
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    • 2000
  • The purpose of this study was to develop a critical pathway for case management of patients who have received Lumbar Laminectomy because of low back pain, arm and leg numbness, and radiating pain in the leg. For this study, a preliminary critical pathway was developed through a review of the literature including five critical pathways which are currently being used in the USA. In order to identify the overall service contents required by these patients, 30 cases were analyzed. These cases were taken from medical records of those with Lumbar Laminectomy between January, 1998 and December, 1998 in the department of neurosurgery at the Pusan National University Hospital in Pusan. An expert validity test was done for the preliminary critical pathway, a clinical validity test was also done using 12 patients with Lumbar Laminectomy between October 1, 1999 and January 31, 2000. After these processes, the final critical pathway was developed. The results are summarized as follows. 1. The vertical axis of the critical pathway includes the following eight items: assessment, consultation, diet, test, medication, treatment, activity, education/ discharge planning. The horizontal axis includes the time from the start of hospitalization to discharge. Analysis of the 30 medical records was done. analysis of the service contents showed the horizontal axis of the preliminary critical pathway was set from hospitalization to the 12th post operation day and the vertical axis was set to include eight items, the contents which should have occurred, according to the time frames of the horizontal axis. 2. As a result of the expert validity test, it was found that among the 233 items, 203 showed over 88% agreement and 30 of them showed less than 88% agreement, which were then revised or deleted from the critical pathway. At the preliminary meeting for the clinical validity test, the time of hospitalization on the horizontal axis was shortened to the 10th post operation day. A clinical validity test was done with 12 patients with Lumbar Laminectomy. All the cases progressed according to the critical pathway although some variances were noted in assessment, consultation, test, medication, and treatment. 3. Based on these results, a final critical pathway was determined. In conclusion, this critical pathway is partially applicable to the care of patients with Lumbar Laminectomy and needs further investigation.

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Gene Microarray Assessment of Multiple Genes and Signal Pathways Involved in Androgen-dependent Prostate Cancer Becoming Androgen Independent

  • Liu, Jun-Bao;Dai, Chun-Mei;Su, Xiao-Yun;Cao, Lu;Qin, Rui;Kong, Qing-Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9791-9795
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    • 2014
  • To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

Characterization of $\beta$-Ketoadipate Pathway from Multi-Drug Resistance Bacterium, Acinetobacter baumannii DU202 by Proteomic Approach

  • Park, Soon-Ho;Kim, Jae-Woo;Yun, Sung-Ho;Leem, Sun-Hee;Kahng, Hyung-Yeel;Kim, Seung-Il
    • Journal of Microbiology
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    • v.44 no.6
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    • pp.632-640
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    • 2006
  • In this study, the biodegradative activities of monocyclic aromatic compounds were determined from the multi-drug resistant (MDR) Acinetobacter baumannii, which were studied in the form of clinical isolates from a hospital in Korea. These bacteria were capable of biodegrading monocyclic aromatic compounds, such as benzoate and p-hydroxybenzoate. In order to determine which pathways are available for biodegradation in these stains, we conducted proteome analyses of benzoate, and p-hydroxybenzoate-cultured A. baumannii DU202, using 2-DE/MS analysis. As genome DB of A. baumannii was not yet available, MS/MS analysis or de novo sequencing methods were employed in the identification of induced proteins. Benzoate branch enzymes [catechol 1,2-dioxygenase (CatA) and benzoate dioxygenase $\alpha$ subunit (BenA)] of the $\beta$-ketoadipate pathway were identified under benzoate culture condition and p-hydroxybenzoate branch enzymes [protocatechuate 3,4-dioxygenas $\alpha$ subunit (PcaG) and 3-carboxy-cis,cis-muconate cycloisomerase (PcaR)] of the $\beta$-ketoadipate pathway were identified under p-hydroxybenzoate culture condition, respectively, thereby suggesting that strain DU202 utilized the $\beta$-ketoadipate pathway for the biodegradation of monocyclic aromatic compounds. The sequence analysis of two purified dioxygenases (CatA and PcaGH) indicated that CatA is closely associated with the CatA of Acinetobacter radiresistance, but PcaGH is only moderately associated with the PcaGH of Acinetobacter sp. ADPI. Interestingly, the fused form of PcaD and PcaC, carboxymuconolactone decarboxylase (PcaCD), was detected on benzoate-cultured A. baumannii DU202. These results indicate that A. baumannii DU202 exploits a different $\beta$-ketoadipate pathway from other Acinetobacter species.

Supervised Model for Identifying Differentially Expressed Genes in DNA Microarray Gene Expression Dataset Using Biological Pathway Information

  • Chung, Tae Su;Kim, Keewon;Kim, Ju Han
    • Genomics & Informatics
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    • v.3 no.1
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    • pp.30-34
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    • 2005
  • Microarray technology makes it possible to measure the expressions of tens of thousands of genes simultaneously under various experimental conditions. Identifying differentially expressed genes in each single experimental condition is one of the most common first steps in microarray gene expression data analysis. Reasonable choices of thresholds for determining differentially expressed genes are used for the next-stap-analysis with suitable statistical significances. We present a supervised model for identifying DEGs using pathway information based on the global connectivity structure. Pathway information can be regarded as a collection of biological knowledge, thus we are trying to determine the optimal threshold so that the consequential connectivity structure can be the most compatible with the existing pathway information. The significant feature of our model is that it uses established knowledge as a reference to determine the direction of analyzing microarray dataset. In the most of previous work, only intrinsic information in the miroarray is used for the identifying DEGs. We hope that our proposed method could contribute to construct biologically meaningful structure from microarray datasets.

Development of a Critical Pathway of Barbiturate Coma Therapy in the Management for Severe Brain Damage (중증 뇌 손상환자를 위한 바비튜레이트 혼수요법의 표준임상지침(Critical Pathway) 개발)

  • Kim, Jung-Sook
    • Journal of Korean Academy of Nursing Administration
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    • v.16 no.1
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    • pp.59-72
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    • 2010
  • Purpose: This study is a descriptive research to analyze prognostic factors of barbiturate coma therapy (BCT) for severe brain damage patients, to develop a critical pathway (CP) based on the results of analysis and to examine the effect of its clinical application. Method: We analyzed medical records of 76 patients who received BCT for more than three days between January 1999 to July 2005. Based on the results of the analysis, we developed a CP and applied it to 12 people during August-December of 2005. Result: By application of BCT CP, the mortality rate decreased from 31.6% to 16.7%. It was found that the period of staying at ICU and total period of hospitalization were shortened by 2.78 (13.9%) days and 16.43 (29.4%) days, respectively. The Glasgow coma scale of the recovery group by CP application was 9.03 (4.64) at 72 hours post of BCT and 14.28 (1.82) at discharge from hospital, and DRS was 6.62 (6.38) points. Conclusion: By verifying clinical validity of the suggested CP, we believe that we have obtained visible effects standardizing the treatment pathway of BCT for brain damage patients.

Analysis of MAPK Signaling Pathway Genes in the Intestinal Mucosal Layer of Necrotic Eenteritis-Afflicted Two Inbred Chicken Lines

  • Truong, Anh Duc;Hong, Yeojin;Lee, Janggeun;Lee, Kyungbaek;Lillehoj, Hyun S.;Hong, Yeong Ho
    • Korean Journal of Poultry Science
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    • v.44 no.3
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    • pp.199-209
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    • 2017
  • Mitogen-activated protein kinase (MAPK) signaling pathways play a key role in innate immunity, inflammation, cell proliferation, cell differentiation, and cell death. The main objective of this study was to investigate the expression level of candidate MAPK pathway genes in the intestinal mucosal layer of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE). Using high-throughput RNA sequencing, we investigated 178 MAPK signaling pathway related genes that were significantly and differentially expressed between the intestinal mucosal layers of the NE-afflicted and control chickens. In total, 15 MAPK pathway genes were further measured by quantitative real-time PCR(qRT-PCR) and the results were consistent with the RNA-sequencing data. All 178 identified genes were annotated through Gene Ontology and mapped onto the KEGG chicken MAPK signaling pathway. Several key genes of the MAPK pathway, ERK1/2, JNK1-3, p38 MAPK, MAP2K1-4, $NF-{\kappa}B1/2$, c-Fos, AP-1, Jun-D, and Jun, were differentially expressed in the two chicken lines. Therefore, we believe that RNA sequencing and qRT-PCR analysis provide resourceful information for future studies on MAPK signaling of genetically disparate chicken lines in response to pathogens.

A Study of the Predictive Effectiveness of Stem and Root Extracts of Cannabis sativa L. Through Network Pharmacological Analysis (네트워크 분석기반을 통한 대마 줄기 및 뿌리 추출물의 약리효능 예측연구)

  • Myung-Ja Shin;Min-Ho Cha
    • Journal of Life Science
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    • v.34 no.3
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    • pp.179-190
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    • 2024
  • Cannabis sativa is a plant widely cultivated worldwide and has been used as a material for food, medicine, building materials and cosmetics. In this study, we assessed the functional effects of C. sativa stem and root extracts using network pharmacology and confirmed their novel functions. The components in stem and root ethanol extracts were identified by gas chromatography-mass spectrometry analysis, and networks between the components and proteins were constructed using the STICHI database. Functional annotation of the proteins was performed using the KEGG pathway. The effects of the extracts were confirmed in lysophosphatidylcholine-induced THP-1 cells using real-time PCR. A total of 21 and 32 components were identified in stem and root extracts, respectively, and 147 and 184 proteins were linked to stem and root components, respectively. KEGG pathway analysis showed that 69 pathways, including the MAPK signaling pathway, were commonly affected by the extracts. Further investigation using pathway networks revealed that terpenoid backbone biosynthesis was likely affected by the extracts, and the expression of the MVK and MVD genes, key proteins in terpenoid backbone biosynthesis, was decreased in LPC-induced THP-1 cells. Therefore, this study determined the diverse function of C. sativa extracts, providing information for predicting and researching the effects of C. sativa.

Effects of a Standardized Critical Pathway for Gastrectomy Patients in a General Hospital (일개 종합병원의 위 절제 환자에 적용한 Critical Pathway의 효과)

  • Kim, Eun-Ok;Kwon, Soon-Man
    • Korea Journal of Hospital Management
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    • v.9 no.3
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    • pp.128-142
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    • 2004
  • To evaluate the effects of critical pathway on the length of hospital stay, the cost and quality of care provided to gastrectomy patients in a tertiary care academic medical center. The basic research design is a retrospective case-control comparative study. 470 patients of gastrectomy were included in the study; 180 before pathway development (control), 163 right after pathway implementation (path group I) and 127 one year after pathway implementation (path groupII). 476 patients of modified radical mastectomy were also analyzed to examine whether the reduction of the length of hospital stay is from the hospital-wide trend or due to the critical pathway. Death after operation, ICU stay, unplanned re-operation, readmission after discharge, the length of hospital stay and cost were analyzed. 2-test, one-way ANOVA, Bonferroni and Turkey's test were used for statistical analysis. (1) There were no significant differences in patient clinical conditions and no sign of deterioration of quality from critical pathway. (2) The length of hospital stay was 13.0 days in control group, 12.2 days in path group I and 10.0 days (p<0.01) in path groupII. (3) The total costs during the hospital stay were reduced. However the cost per day was significantly increased from reduction of hospital stay (358,488won in control, 366,017won in path group I and 413,220won (p<0.01) in path groupII). Critical pathway reduced the length of hospital stay, total hospital costs and resource utilization without harming quality of patient care.

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Differential Gene Expression Profiling in Human Promyelocytic Leukemia Cells Treated with Benzene and Ethylbenzene

  • Sarma, Sailendra Nath;Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.267-277
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    • 2008
  • Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.